A Live Attenuated Human Metapneumovirus Vaccine Strain Provides Complete Protection against Homologous Viral Infection and Cross-Protection against Heterologous Viral Infection in BALB/c Mice

A live attenuated vaccine candidate strain (M2) of human metapneumovirus (hMPV) was generated by removing the N-linked carbohydrate at amino acid 172 in the fusion (F) protein. Previously, replication of M2 in mouse lungs could be detected by molecular assays but not by viral titration. In the present study, the protective effects of M2 against infection by homologous or heterologous viruses were evaluated in BALB/c mice. Immunization with M2 produced a high titer of serum virus-neutralizing antibodies in BALB/c mice at 4 and 8 weeks postimmunization, with the titers against the homologous virus being higher than those against the heterologous virus. Challenges at 4 and 8 weeks postinoculation with M2 or wild-type virus led to no replication when mice were challenged with a homologous virus and extremely reduced replication when mice were challenged with a heterologous virus, as determined by the detection of viral genomic RNA copies in the lungs, as well as significantly milder pulmonary pathology. Thus, M2, with only one N-linked carbohydrate removed in the F protein, provides complete protection from homologous virus infection and substantial cross-protection from heterologous virus infection for at least 56 days after inoculation. This vaccine strain may therefore be a candidate for further preclinical study. Furthermore, this attenuating strategy (changing the glycosylation of a major viral protein) may be useful in the development of other viral vaccines.